Exposure to multiple chemicals in the environment during critical fetal and childhood development periods is an important yet understudied area of public health, particularly when coupled with psychosocial risk factors that may modify the effects of these exposures. To address this gap, the Center for Research on Early Childhood Exposure and Development in Puerto Rico (CRECE) will study the impact of a mixture of environmental exposures and modifying factors on fetal and early childhood health and development in the children of the heavily-contaminated northern coast of Puerto Rico, an underserved, highly-exposed, and low-income population with significant health disparities. To achieve this timely and significant goal, CRECE has developed an innovative and scientifically distinct program that leverages the ongoing cohort study of the PROTECT NIEHS Superfund Research Center; this cohort is following 1800 pregnant Puerto Rican women through childbirth to investigate the relationship between groundwater contamination and the island's extremely high preterm birth rate. CRECE will initiate a follow-up study of 600 infants born to the PROTECT cohort, for whom a rich prenatal dataset and biological samples already exists, following them from birth to age four. Through a unique and holistic source-to-outcome strategy incorporating three interrelated and transdisciplinary research projects and three cores, CRECE will 1) capture the impacts of pollutant exposures (both alone and in combination) that occur through multiple exposure routes and biological pathways on fetal and early childhood health and development, 2) evaluate how psychosocial risk factors (e.g. socioeconomic status and maternal stress) may modify these effects, and 3) elucidate biological mechanisms that may explain mechanistic pathways and mediate these relationships. The CRECE interdisciplinary team includes environmental epidemiologists, pediatricians, environmental scientists/engineers, exposure scientists, sociologists, social workers, biostatisticians, toxicologists, and communication neuroscientists (many of whom have previously collaborated through PROTECT). CRECE will answer important research questions: What are the combined effects of intrauterine and early childhood exposure to multiple pollutants on children's health and development in a highly exposed population? What are the mechanisms by which these effects occur? How do psychosocial factors modify the effects of environmental chemical exposures? Can exposure biomarkers be developed to capture multi- pollutant and multi-pathway exposures for health effect investigations? The answers to these questions, along with the innovative tools and methods developed to answer them, will advance the science of children's environmental health by improving our understanding of the effects of the total environment on at-risk as well as general populations with multiple exposures. The proposed work will inform future clinical intervention, risk assessment, and policy-setting efforts for both this at-risk, vulnerable population and the U.S. as a whole.